The leading causes of vision impairment (e.g., low vision and blindness) in older Americans include macular degeneration, glaucoma, cataract and diabetic retinopathy. Age-related visual impairment is second only to arthritis/rheumatism as a cause of disability. Vision loss ranks third below arthritis and heart disease as a top cause of impaired daily functioning in people over the age of 70. The projections are that, by 2020, as many as 5.5 million Americans will suffer from low vision or blindness.
Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye, causing it to thicken and swell. It contributes to vision loss by altering the functional cell relationship in the retina and promoting an inflammatory reparative response. Macular edema may be intracellular or extracellular. Extracellular accumulation of fluid, which is more frequent and clinically more relevant, is directly associated with an alteration of the blood-retinal barrier (BRB).
Macular edema may be caused by retinal vein occlusions (RVOs). RVOs are known as retinal vascular disorders characterized by engorgement and dilatation of the retinal veins with secondary, mostly intraretinal hemorrhages and mostly intraretinal (and partially subretinal) edema, retinal ischemia, and macular edema. RVOs include central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO).
Various approaches have been documented in attempting to manage CRVO. Grid laser treatment has shown poor efficacy in treating CRVO. Intravitreal injection of steroids led to several undesirable side effects such as cataract or secondary ocular hypertension. Intravitreal injection of anti-VEGF agents has shown promises in treating macular edema of different origins. However, such intervention is considered invasive. Furthermore, patients may need regular injections. In many cases, moreover, they need to continue to receive such treatments for the rest of their lives.
Diabetic macular edema (DME), a retinal thickening involving the center of the macula, represents the most common cause of vision loss in patients affected by diabetes mellitus. DME occurs in approximately 14% of diabetics. The incidence of diabetic macular edema is closely associated with the degree of diabetic retinopathy and the duration and type of the disease. Diabetic retinopathy results from the inner blood-retinal barrier being compromised, which leads to leakage of plasma constituents in the surrounding retina. Vision loss due to diabetic retinopathy may result from several mechanisms. Macular edema or capillary nonperfusion may directly impair central vision.
Fewer than 10% type II diabetic patients have DME five years after the diagnosis of diabetes, while close to 30% suffer from DME 20 years after the diagnosis. For type I diabetic patients the incident of DME is low in the first five years but is close to 30% 20 years after the diagnosis. Patients treated with insulin have a higher risk of developing macular edema. Photocoagulation is the standard of care for diabetic macular edema. However, many patients are unresponsive to laser therapy and fail to improve after photocoagulation. Current interventions also include the intravitreal administration of steroids. However it may lead to a significant increase in intraocular pressure.
Patients with diabetic macular edema have been found to have increased levels of VEGF in the vitreous. Thus, potent and specific anti-VEGF drugs have become common treatment of diabetic macular edema. On the other hand, the frequent injections for a presumably extended period that may be required with the currently available anti-VEGF drugs, make injection-related complications such as infectious endophthalmitis a drawback.
Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. In the US alone, there are close to 10 million patients suffering from AMD, close to 2 million have advanced AMD, which is also called wet AMD. The other form of AMD is called dry AMD, which is an early stage of the disease and may result from the aging and thinning of macular tissues, depositing pigment in the macula, or a combination of the two processes.
For generalized health problems such as diabetes or high blood pressure, it is evident that systemic medical therapy should be considered first and foremost. However, systemic approach has fallen to the sideline when it comes to treating retinal disorders. This is simply due to their poor bioavailability in retina when products are taken systemically. In addition, in order to have a therapeutic level of product in retina, higher dose must be taken which may lead to systemic toxicity.